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肺肉瘤样癌中NANOG表达及上皮-间质转化的免疫组织化学分析

Immunohistochemical analysis of NANOG expression and epithelial-mesenchymal transition in pulmonary sarcomatoid carcinoma.

作者信息

Tamaki Takeshi, Shimizu Toshiki, Niki Maiko, Shimizu Michiomi, Nishizawa Tohru, Nomura Shosaku

机构信息

First Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan.

出版信息

Oncol Lett. 2017 May;13(5):3695-3702. doi: 10.3892/ol.2017.5864. Epub 2017 Mar 16.

Abstract

Pulmonary sarcomatoid carcinomas (PSCs) are defined as a group of poorly differentiated non-small cell lung cancers that demonstrate sarcoma-like differentiation. The mechanism of mesenchymal differentiation in PSC is epithelial-mesenchymal transition (EMT). The expression of homeobox protein NANOG (NANOG), which regulates the pluripotency of embryonic stem cells, is associated with the EMT process. Therefore, the present study aimed to assess the expression level of NANOG and the status of the EMT process in PSC. The data of patients with PSC were retrospectively reviewed and immunohistochemical analyses were performed on patient samples to examine the expression of NANOG and EMT-associated proteins. The comparator group included randomly selected patients with matched clinicopathological characteristics who had pulmonary adenocarcinoma (PA). In the present study, 12 patients with PSC (4 females and 8 males) were enrolled; their median age was 65 years (range, 36-79 years), and the number of patients with stage IB, IIB, IIIA, IIIB and IV disease were 1, 1, 1, 1 and 8, respectively. The immunoreactive score (IRS) for E-cadherin was significantly lower in the PSC group compared with the PA group (P<0.0001), whereas the IRS for vimentin was significantly higher in the PSC group compared with the PA group (P<0.0001). However, the IRS for NANOG was significantly decreased in the PSC group compared with the PA group (P<0.0001), which suggests that NANOG does not serve an essential role in EMT in PSC. In addition, the overall survival of patients with PSC was significantly lower compared with that of patients with PA (median survival time, 7.0 vs. 35.6 months, respectively; P=0.0256). However, no significant difference was observed in the OS of patients who expressed low compared with high levels of NANOG (P=0.4416). In conclusion, it was clearly demonstrated that cytoplasmic NANOG expression was significantly lower in PSC compared with PA, and that the EMT process in PSC was accelerated, compared with that in PA.

摘要

肺肉瘤样癌(PSCs)被定义为一组具有肉瘤样分化的低分化非小细胞肺癌。PSC中间充质分化的机制是上皮-间质转化(EMT)。调控胚胎干细胞多能性的同源盒蛋白NANOG(NANOG)的表达与EMT过程相关。因此,本研究旨在评估PSC中NANOG的表达水平及EMT过程的状态。对PSC患者的数据进行回顾性分析,并对患者样本进行免疫组化分析,以检测NANOG和EMT相关蛋白的表达。对照组包括随机选取的具有匹配临床病理特征的肺腺癌(PA)患者。本研究纳入了12例PSC患者(4例女性,8例男性);他们的中位年龄为65岁(范围36 - 79岁),IB期、IIB期、IIIA期、IIIB期和IV期疾病的患者人数分别为1例、1例、1例、1例和8例。与PA组相比,PSC组中E-钙黏蛋白的免疫反应评分(IRS)显著降低(P<0.0001),而PSC组中波形蛋白的IRS显著高于PA组(P<0.0001)。然而,与PA组相比,PSC组中NANOG的IRS显著降低(P<0.0001),这表明NANOG在PSC的EMT中不起关键作用。此外,PSC患者的总生存期显著低于PA患者(中位生存时间分别为7.0个月和35.6个月;P = 0.0256)。然而,NANOG表达水平低与高的患者的总生存期无显著差异(P = 0.4416)。总之,明确表明与PA相比,PSC中细胞质NANOG表达显著降低,且与PA相比,PSC中的EMT过程加速。

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